Presynaptic Receptors and Modulation of Noradrenaline and ATP Secretion from Sympathetic Nerve Varicositiesa

: Our results in the model tissues examined show (1) that alpha 2 agonist(s) depressed the secretion of NA and ATP caused by nerve stimulation at low frequency, (2) that the secretion of both NA and ATP was moderately autoinhibited, under conditions when endogenous NA was shown to accumulate extracellularly, (3) that a K+ channel blocking agent increased much more strongly than alpha 2-adrenoceptors block the secretion of both NA and ATP, and also amplified enormously the NA-mediated neurogenic contraction, (4) that, therefore, a high K+ efflux is likely to be much more important than alpha 2-adrenoceptor-mediated autoinhibition for maintaining a low release probability in sympathetic nerve varicosities, and (5) that the alpha 2-adrenoceptor agonist, clonidine, or the Ca2+ channel blocking agent, Cd2+, inhibited transmitter secretion, at least in part, via targets "upstream" of the varicosity.